LaTonya J. Hickson a,b,c,1 , Larissa G.P. Langhi Prata a,1 , Shane A. Bobart c , Tamara K. Evans a,d , Nino Giorgadze a , Shahrukh K. Hashmi a,e , Sandra M. Herrmann c , Michael D. Jensen f , Qingyi Jia f , Kyra L. Jordan c , Todd A. Kellogg g , Sundeep Khosla a,f , Daniel M. Koerber a , Anthony B. Lagnado a,h , Donna K. Lawson i , Nathan K. LeBrasseur a,j,k , Lilach O. Lerman c , Kathleen M. McDonald a,l , Travis J. McKenzie g , João F. Passos a,h , Robert J. Pignolo a,b,f,i,j , Tamar Pirtskhalava a , Ishran M. Saadiq c , Kalli K. Schaefer a , Stephen C. Textor c , Stella G. Victorelli a,h , Tammie L. Volkman a,d , Ailing Xue a , Mark A. Wentworth a,l , Erin O. Wissler Gerdes a,d , Yi Zhu a , Tamara Tchkonia a, ⁎, James L. Kirkland a,b,i,m, ⁎

a Cellular Senescence and Translation and Pharmacology Programs, Robert and Arlene Kogod Center on Aging, Mayo Clinic, United States of America

b Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, United States of America

c Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, United States of America

d Department of Medicine Clinical Trials Unit, Department of Medicine, Mayo Clinic, United States of America

e Division of Hematology, Department of Medicine, Mayo Clinic, United States of America

f Division of Endocrinology, Department of Medicine, Mayo Clinic, United States of America

g Department of Surgery, Mayo Clinic, United States of America

h Department of Physiology and Biomedical Engineering, Mayo Clinic, United States of America

i Division of Hospital Medicine, Department of Medicine, Mayo Clinic, United States of America

j Department of Physiology, Mayo Clinic, United States of America

k Department of Physical Medicine and Rehabilitation, Mayo Clinic, United States of America

l Office of Research Regulatory Support, Mayo Clinic, United States of America

m Division of General Internal Medicine, Department of Medicine, Mayo Clinic, United States of America

article info

Article history:

Received 31 July 2019

Received in revised form 16 August 2019

Accepted 29 August 2019

Keywords:

Senolytics

Cellular senescence

Dasatinib

Quercetin

Diabetic kidney disease

Senescence-associated secretory phenotype

Corresponding authors at: Cellular Senescence Program, Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, United States of America.

E-mail addresses: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (T. Tchkonia), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.L. Kirkland).

1 These authors contributed equally.

https://doi.org/10.1016/j.ebiom.2019.08.069

2352-3964/© 2019 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Derrick J. Rossi,1, * Catriona H.M. Jamieson,2 and Irving L. Weissman3

1Immune Disease Institute, Harvard Stem Cell Institute, and the Department of Pathology, Harvard Medical School, Boston, MA 02115, USA

2Moores Cancer Center, Division of Hematology/Oncology and Department of Medicine, University of California, San Diego, CA 92093, USA

3Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Cancer Center, and Department of Pathology,

Stanford University School of Medicine, Stanford, CA 94305-5323, USA

*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

DOI 10.1016/j.cell.2008.01.036

The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Here, we examine evidence linking stem cell dysfunction to the pathophysiological conditions accompanying aging, focusing on the mechanisms underlying stem cell decline and their contribution to disease pathogenesis.

Ameya S. Kulkarni,1,2, * Sriram Gubbi,3 and Nir Barzilai1,2

1Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY, USA

2Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York, NY, USA

3Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (A.S.K.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (N.B.)

https://doi.org/10.1016/j.cmet.2020.04.001

Biological aging involves an interplay of conserved and targetable molecular mechanisms, summarized as the hallmarks of aging. Metformin, a biguanide that combats age-related disorders and improves health span, is the first drug to be tested for its age-targeting effects in the large clinical trial—TAME (targeting aging by metformin). This review focuses on metformin’s mechanisms in attenuating hallmarks of aging and their interconnectivity, by improving nutrient sensing, enhancing autophagy and intercellular communication, protecting against macromolecular damage, delaying stem cell aging, modulating mitochondrial function, regulating transcription, and lowering telomere attrition and senescence. These characteristics make metformin an attractive gerotherapeutic to translate to human trials.

Subodh Kumar a,**, Hallie Morton a , Neha Sawant a , Erika Orlov a , Lloyd E Bunquin a , Jangampalli Adi Pradeepkiran a , Razelle Alvir a , P. Hemachandra Reddy a , b ,c,d,e,

a Internal Medicine Department, Texas Tech University Health Sciences Center, Lubbock, TX, USA

b Neuroscience & Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX, USA

c Neurology Departments School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

d Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA

e Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX, USA

ARTICLE INFO

Keywords: Alzheimer’s disease     MicroRNA-455-3p   Mouse models   Mitochondrial biogenesis   Synaptic activity

ABSTRACT

Background: MicroRNA-455-3p is one of the highly conserved miRNAs involved in multiple cellular functions in humans and we explored its relevance to learning and memory functions in Alzheimer’s disease (AD). Our recent in vitro studies exhibited the protective role of miR-455-3p against AD toxicities in reducing full-length APP and amyloid-β (Aβ) levels, and also in reducing defective mitochondrial biogenesis, impaired mitochondrial dynamics and synaptic deficiencies. In the current study, we sought to determine the function of miR-455-3p in mouse models. 

Methods: For the first time we generated both transgenic (TG) and knockout (KO) mouse models of miR-455-3p. We determined the lifespan extension, cognitive function, mitochondrial biogenesis, mitochondrial dynamics, mitochondrial morphology, dendritic spine density, synapse numbers and synaptic activity in miR-455-3p TG and KO mice.

Results: MiR-455-3p TG mice lived 5 months longer than wild-type (WT) counterparts, whereas KO mice lived 4 months shorter than WT mice. Morris water maze test showed improved cognitive behavior, spatial learning and memory in miR-455-3p TG mice relative to age-matched WT mice and miR-455-3p KO mice. Further, mitochondrial biogenesis, dynamics and synaptic activities were enhanced in miR-455-3p TG mice, while these were reduced in KO mice. Overall, overexpressed miR-455-3p in mice displayed protective effects, whereas depleted miR-455-3p in mice exhibited deleterious effects in relation to lifespan, cognitive behavior, and mitochondrial and synaptic activities.

Conclusion: Both mouse models could be ideal research tools to understand the molecular basis of aging and its relevance to AD and other age-related diseases.

* Corresponding author. Internal Medicine, Cell Biology & Biochemistry, Neuroscience & Pharmacology, Neurology, Public Health and School of Health Professions, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, United States.

** Corresponding author. Internal Medicine Department, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, United States. E-mail addresses: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S. Kumar), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (P.H. Reddy).

https://doi.org/10.1016/j.redox.2021.102182

Received 14 October 2021; Received in revised form 2 November 2021; Accepted 6 November 2021

Available online 9 November 2021

2213-2317/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).